Amylyx Pharmaceuticals is making strides in its clinical pipeline, highlighted by positive Phase 2 data for AMX0035 in Wolfram syndrome and the planned initiation of a Phase 3 trial for avexitide in post-bariatric hypoglycemia (PBH). These advancements, coupled with ongoing research in amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP), underscore Amylyx's commitment to addressing unmet needs in neurodegenerative and endocrine disorders.
Positive Phase 2 Results for AMX0035 in Wolfram Syndrome
The Phase 2 HELIOS trial, an open-label study involving 12 adults with Wolfram syndrome, demonstrated that AMX0035 (sodium phenylbutyrate and taurursodiol) led to improvements in pancreatic function, the trial's primary efficacy endpoint, as measured by C-peptide response after 24 weeks. Wolfram syndrome, a rare, progressive, monogenic disease affecting approximately 3,000 people in the U.S., typically results in a decline in pancreatic function over time. Secondary endpoints, including hemoglobin A1c (HbA1c), time in target glucose range, and visual acuity, also showed overall improvements or stabilization. The safety profile of AMX0035 in the HELIOS trial was consistent with previous data. Amylyx is engaging with stakeholders and plans to meet with the FDA to discuss a Phase 3 program, with updates expected in 2025.
Avexitide for Post-Bariatric Hypoglycemia
Amylyx's acquisition of avexitide, a glucagon-like peptide-1 (GLP-1) receptor antagonist, positions the company to address hyperinsulinemic hypoglycemia. Avexitide has received FDA Breakthrough Therapy Designation and Orphan Drug Designation for hyperinsulinemic hypoglycemia. Clinical trials have evaluated avexitide in PBH and congenital hyperinsulinism (HI). Phase 2 studies in PBH have shown statistically significant reductions in hypoglycemia events. Amylyx is on track to initiate a Phase 3 program for avexitide in PBH in the first quarter of 2025, with topline data anticipated in 2026. Symptomatic PBH affects approximately 8% of people who have undergone bariatric surgery, characterized by an excessive GLP-1 response, dysregulated insulin secretion, and a rapid drop in blood sugar. It is estimated that ~160,000 people are currently living with symptomatic PBH in the U.S., classifying it as an orphan condition.
Advancing ALS Research with AMX0114
Amylyx is also advancing its research in ALS with AMX0114, an antisense oligonucleotide targeting calpain-2. The company plans to initiate the Phase 1 LUMINA clinical trial of AMX0114 in people living with ALS by the end of 2024 or in early 2025 in Canada. The FDA has requested additional information, resulting in a clinical hold in the U.S., but Amylyx believes the trial can be completed outside of the U.S. if needed. Early cohort data from LUMINA are expected in 2025. AMX0114 is designed to inhibit calpain-2, a protease implicated in the pathogenesis of ALS. Preclinical studies have shown that AMX0114 reduces extracellular neurofilament light chain levels and improves survival of iPSC-derived human motor neurons harboring ALS-linked TDP-43 mutations.
Financial Position
As of September 30, 2024, Amylyx reported cash, cash equivalents, and marketable securities of $234.4 million, providing a cash runway into 2026. This financial stability supports the company's ongoing clinical trials and research programs.
